RNAPol2 accounts for tumor cells liability to JQ1 [Affymetrix]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE76188 | GEO | 2016/08/25
SECONDARY ACCESSION(S): PRJNA306757
REPOSITORIES: GEO
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Project description:We here use B-cell tumors as a model to address the mechanism of action of JQ1, a widely used BET inhibitor.
2016-08-25 | GSE76191 | GEO
Project description:RNAPol2 accounts for tumor cells liability to JQ1
| PRJNA306755 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-08-25 | GSE76192 | GEO
Project description:ChIP-Seq of RNA Polymerase II, and transcriptional regulators in multiple myeloma (MM.1S), glioblastoma (U87-MG), and small cell lung carcinoma (H2171) treated with the BET bromodomain inhibitor JQ1. Cell lines (MM.1S, U87-MG, and H2171) representing multiple myeloma, glioblastoma, and small cell lung carcinoma, were treated with varying concentrations (5nM to 5µM) of the BET bromodomain inhibitor JQ1 followed by ChIP-Seq for RNA Polymerase II and transcriptional regulators. Other datasets from this series of experiments have been release as a part of GSE42355.
2013-07-26 | E-GEOD-49224 | biostudies-arrayexpress
Project description:BET bromodomain inhibitors are emerging as very promising novel anticancer agents. Combination of BET bromodomain inhibitor JQ1 and quinone-containing compound nanaomycin exerts synergistic anticancer effect in neuroblastoma We analysed whether a treatment with BET bromodomain inhibitor JQ1, and quinone-containing compound Nanaomycin synergistically modulate gene expression
2016-12-31 | GSE76066 | GEO
Project description:Recent findings have shown that inhibitors targeting BET (bromodomain and extraterminal domain) proteins, such as the small molecule JQ1, are potent growth inhibitors of many cancers and hold promise for cancer therapy. However, some reports also have revealed that JQ1 can activate additional oncogenic pathways and may affect EMT (epithelial mesenchymal transition). Therefore, it is important to address the potential unexpected effect of JQ1 treatment, such as cell invasion and metastasis. Here, we showed that in prostate cancer, JQ1 inhibited cancer cell growth but promoted invasion and metastasis in a BET protein independent manner. Multiple invasion pathways including EMT, BMP (bone morphogenetic protein) signaling, chemokine signaling and focal adhesion pathway were activated by JQ1 to promote invasion. Notably, JQ1 induced upregulation of invasion genes through inhibition of FOXA1, an invasion suppressor in prostate cancer. JQ1 directly interacted with FOXA1, inactivated FOXA1 binding to its interacting repressors, TLE3, HDAC7 and NFIC, thus blocking FOXA1 repressive function and activating the invasion genes. Our finding indicates that JQ1 has an unexpected effect of promoting invasion in prostate cancer. Thus, the ill effect of JQ1 or its derived therapeutic agents could not be ignored during cancer treatment, especially in FOXA1 related cancers.
2022-10-01 | GSE139230 | GEO
Project description:Selective bromodomains inhibitors block the interaction between diverse bromodomains and extraterminal domains (BET) proteins and acetylated proteins. These inhibitors have shown beneficial effects in cancers malignancies and experimental inflammation in mouse models, but data on renal diseases are scarce. We have investigated the effect of the BET proteins inhibitor JQ1 in a mice model of unilateral ureteral obstruction. Treatment with JQ1 diminished renal damage, the presence of inflammatory cell infiltration and the upregulation of proinflammatory genes. The in vitro evaluation of JQ1 on TNF-α inducible genes in renal cells showed that BET inhibition modulated several biological processes, including inflammation or immune response. Moreover, gene-silencing experiments showed that BRD4 regulates several proinflammatory genes (IL-6, CCL-2 and CCL-5) and chromatin immunoprecipitation techniques demonstrated that BRD4 specifically binds to acetylated histone H3 in the promoter region of those genes. The nuclear factor-ï«B (NF-ï«B) pathway regulates renal inflammation. The RelA NF-ï«B subunit is activated by acetylation of lysine 310. In damaged kidneys and in TNF-α-treated renal cells, JQ1 blocked the nuclear translocation of RelA/NF-ï«B and NF-ï«B-mediated gene expression. Additionally, obstructed kidneys showed an activation of the Th17 immune response, which was diminished by JQ1 treatment. Our results demonstrate that the BET inhibition decreases renal inflammation by 3 independent mechanisms: 1) chromatin remodelling in the promoter regions of specific genes, 2) blocking NF-ï«B pathway activation, and 3) modulating the Th17 immune response. These results suggest that BET inhibitors could have important therapeutic applications in inflammatory renal diseases. HK2 cell line was treated with JQ1 or its enantiomer JQ1(-) (500nM) for 1 hour before stimulation or not with TNF-α (5ng/ml) for additional 3h. We analized the genes up- and down-regulated by TNF-α vs unstimulated cells, and further the genes downregulated or unaffected by JQ1 compared to the cells treated with the enantiomer (-) JQ1.
2016-07-01 | E-GEOD-71602 | biostudies-arrayexpress
Project description:BET bromodomain inhibitors effectively kill several types of cancer cells. However, the underlying mechanism of BET inhibition resistance remains obscure. We sought to identify the gene expression change upon treatment of JQ1, a well-known BET inhibitor, in basal-like breast cancer cells. In this dataset, we used RNA-sequencing to characterize the mRNA expression profiles from DMSO and JQ1-treated MDA-MB-231 breast tumor cells.
2019-11-07 | GSE140003 | GEO
Project description:The bromodomain and extra terminal domain (BET) family of proteins, including BRD2, BRD3, and BRD4, play a key role in many cellular processes, including inflammatory gene expression, mitosis, and viral/host interaction by controlling the assembly of histone acetylation-dependent chromatin complexes. Previous studies have shown that multiple BET inhibitors (BETi), including JQ1, have therapeutic effects in cancer and cardiovascular diseases. Some BETi have entered different phases of clinical trials. Pharmacologically, JQ1 functions by displacing BET proteins from chromatin by competitively binding to the acetyl-lysine recognition pocket of BET bromodomains. JQ1 has been used as a chemical probe to investigate the role of BET bromodomains in the transcriptional regulation of cardiovascular diseases. For example, JQ1 has been shown to attenuates inflammation and experimental atherosclerosis (Mol Cell. 2014 Oct 23; 56(2): 219–231.). JQ1 has also recently been shown to reduce EndoMT and cardiac fibrosis (J Mol Cell Cardiol. 2019 Feb;127:83-96.). However, the molecular targets of JQ1 dependent or independent of BRD4 remains unknown. To depict the transcriptomic signature of JQ1 in human endothelial cells, we observed a vasoprotective and atheroprotective transcriptome by JQ1 treatment using genome-wide RNA-seq based transcriptomic profiling. JQ1 is a magic bullet in cardiovascular disease prevention. Further elucidation of new molecular targets of JQ1 will lead to the identification of potentially new therapeutic targets to treat cardiovascular diseases.
2019-11-27 | GSE137500 | GEO
Project description:We performed RNA sequencing (RNA-seq) of HNSCC cells to examine genome-wide gene expression pattern following JQ1 treatment. BET inhibition by JQ1 significantly inhibits a cohort of key oncogenes associate with tumorigenesis and metastasis. Suggesting BET inhibition is effective strategy to suppress the tumorigenesis and metastasis of head and neck squamous cell carcinoma.
2021-05-05 | GSE131967 | GEO